期刊
CANCER BIOLOGY & THERAPY
卷 21, 期 6, 页码 570-580出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2020.1739952
关键词
Chimeric antigen receptor T; prostate cancer; prostate specific membrane antigen; xenograft; effector cells
类别
资金
- Natural Science Foundation of Xinjiang Uygur Autonomous Region [2018D01C177]
Objective: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated an unprecedented therapeutic efficacy in hematological malignancies; however, its effectiveness in solid tumors remains elusive. In order to enable CAR-T cells more effective to solid tumors, a inverted chimeric cytokine receptor (ICR) was designed, which is consists of the TGF-beta extracellular domain, IL-7 receptor intracellular domain, and co-expression on CAR-T cells. Materials and Methods: We selected prostate specific membrane antigen (PSMA) as a target for CAR-T cells, constructed corresponding effector cells, and verified the anti-tumor activity of this enhanced PSMA-CAR-T cell by a series of repeated target cell stimulation experiments in vitro and the anti-tumor capabilities by using mice xenograft model in vivo. Results: In vitro experiments showed that co-expression of ICR could significantly enhance sustained anti-tumor capabilities of PSMA-CAR-T cells. Moreover, in vivo experiments also confirmed that the enhanced PSMA-CAR-T cells exhibited significant superior anti-tumor capabilities and could prolong the survival time in the xenograft and PDX models of prostate cancer. Conclusions: PSMA-CAR-T cells co-expressing ICR can be envisaged as a new therapeutic strategy for prostate cancer and support the translation of this enhanced approach in the clinical setting.
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